Document Detail


Induction of senescence in human malignant glioma cells by p16INK4A.
MedLine Citation:
PMID:  9247304     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
p16INK4A is a G1-specific cell cycle inhibitor which maps to human chromosome 9p21, a region frequently mutated or deleted in cancer cell lines and primary tumors. In glioblastomas the frequency of homozygous deletions is 40-70% making it one of the most common mutations in this tumor type. We have analysed the significance of the loss of this gene in gliomas by introducing the cDNA for p16INK4A into the human glioma cell line U-1242 MG which has a deleted CDKN2 locus. We used the tetracycline repressible vector system and obtained two stably transfected clones that expressed p16INK4A upon induction. p16INK4A expression caused a G1 arrest and enlargement of the cells similar to that of senescent cells. When staining for Senescence-Associated beta-galactosidase activity, described to be specific for senescent cells, we could show that the enlarged cells specifically gave a positive staining reaction. This senescence phenotype was dependent on the continuous expression of p16INK4A since it was reversed upon reintroduction of tetracycline suppression. Thus, the induced expression of p16INK4A in these glioma cells reverted their immortal phenotype and caused an immediate cellular senescence.
Authors:
L Uhrbom; M Nistér; B Westermark
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  15     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1997 Jul 
Date Detail:
Created Date:  1997-08-28     Completed Date:  1997-08-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  505-14     Citation Subset:  IM    
Affiliation:
Department of Pathology, Uppsala University, University Hospital, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / genetics
Carrier Proteins / genetics*,  metabolism
Cell Aging / genetics
Cell Division / genetics
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinases / genetics,  metabolism
G1 Phase / genetics
Gene Deletion
Gene Expression Regulation, Neoplastic
Genetic Vectors
Glioma / drug therapy,  genetics*
Homozygote
Humans
Phenotype
Proto-Oncogene Proteins*
Retinoblastoma Protein / genetics,  metabolism
Tetracycline / pharmacology
Vimentin / metabolism
beta-Galactosidase / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Proto-Oncogene Proteins; 0/Retinoblastoma Protein; 0/Vimentin; 60-54-8/Tetracycline; EC 2.7.1.37/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 3.2.1.23/beta-Galactosidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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